Investigating Life

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investigating life

How does knowledge of the genetic code help us understand the actions of some antibiotics?

MRSA can be treated if detected early. Sequencing the DNA of the bacteria can be used to detect mutations and predict the severity of the infection. Antibiotics such as tetracyclines, which target bacterial protein synthesis, are effective in some strains. Tetracyclines kill bacteria by interrupting translation, binding to the small subunit of bacterial ribosomes so that charged tRNA cannot bind to the A site on the ribosome. Tetracyclines do not kill eukaryotic cells, because eukaryotic ribosomes have different proteins and RNAs that do not offer a binding site for tetracyclines.

Whether tetracyclines will continue to offer a viable treatment for MRSA, however, is in doubt. Some strains of MRSA are already resistant to tetracyclines, having acquired genes that convey resistance through bacterial conjugation. The DNA of S. aureus has been altered through acquisition of genes from a plasmid so important that it has been given its own name, the resistome. As with methicillin resistance, the alleles of the resistome encode a ribosomal protein with an altered amino acid sequence that consequently does not bind the antibiotic.

Can you think of other ways to target protein synthesis in MRSA?

Future directions

While the expression of protein-coding genes has been well worked out, recent analyses of eukaryotic genomes show that a lot of transcription remains unaccounted for. International cooperation among laboratories in huge projects such as ENCODE (Encyclopedia of DNA Elements) has revealed, for example, that up to 70 percent of human DNA is transcribed at some point in some cells. With only 2 to 3 percent of DNA consisting of protein-coding genes, the question immediately arises as to what purpose the rest of the RNAs serve. A small fraction are tRNAs and rRNAs, and you will see in Chapter 16 that some of these noncoding RNAs are small (< 200 nucleotides) and have roles in regulating the expression of protein-coding genes. The roles of the longer RNAs (> 200 nucleotides) are much less clear. In humans, over 25,000 of the longer RNAs have been identified. They have much in common with mRNAs: they are transcribed using the same RNA polymerase, undergoing poly A addition, capping at the 5′ and 3′ ends, and splicing. However, the longer RNAs are not as long as mRNAs and are not translated at the ribosome. Some never leave the nucleus, where they may be involved in pre-mRNA events such as transcription and splicing. Others actually arrive at the ribosome, where they may regulate the translation of particular mRNAs. These longer untranslated RNAs are found in many organisms, indicating that they must have important roles that have been selected for in evolution.